Hindawi Publishing Corporation

Journal of Nutrition and Metabolism

Volume 2014, Article ID 202759, 6 pages
http://dx.doi.org/10.1155/2014/202759

Review Article
Nutrigenomics: Definitions and Advances of This New Science

N. M. R. Sales,1 P. B. Pelegrini,2 and M. C. Goersch3

1
Universidade Anhembi Morumbi/Gerencia de Nutricao Enteral e Parenteral, Rua Pedro Ivo 22, 01323-070 Sao Paulo, SP, Brazil
2
BioLife Brasil Ltda, Distrito Agroindustrial de Formosa, Quadra 01, Lote 15, 73801-970 Formosa, GO, Brazil
3
Gerencia de Nutricao Enteral e Parenteral-GANEP, Rua Pedro Ivo 22, 01323-070 Sao Paulo, SP, Brazil

Correspondence should be addressed to P. B. Pelegrini; pbpelegrini@gmail.com

Received 19 November 2013; Revised 20 February 2014; Accepted 27 February 2014; Published 25 March 2014

Academic Editor: M. Meydani

Copyright 2014 N. M. R. Sales et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The search for knowledge regarding healthy/adequate food has increased in the last decades among the world population,
researchers, nutritionists, and health professionals. Since ancient times, humans have known that environment and food can
interfere with an individuals health condition, and have used food and plants as medicines. With the advance of science, especially
after the conclusion of the Human Genome Project (HGP), scientists started questioning if the interaction between genes and food
bioactive compounds could positively or negatively influence an individuals health. In order to assess this interaction between genes
and nutrients, the term Nutrigenomics was created. Hence, Nutrigenomics corresponds to the use of biochemistry, physiology,
nutrition, genomics, proteomics, metabolomics, transcriptomics, and epigenomics to seek and explain the existing reciprocal
interactions between genes and nutrients at a molecular level. The discovery of these interactions (gene-nutrient) will aid the
prescription of customized diets according to each individuals genotype. Thus, it will be possible to mitigate the symptoms of
existing diseases or to prevent future illnesses, especially in the area of Nontransmissible Chronic Diseases (NTCDs), which are
currently considered an important world public health problem.

1. Introduction Therefore, Nutrigenomics is the area of nutrition that uses

Food intake and the environment are the two main factors
that affect the health or illness of an individual [1]. Studies in
nutritional area have increased the understanding of how to
maintain healthy a group of individuals that live in different
dietary conditions [24]. However, after the conclusion of the
Human Genome Project (HGP), new insights about the influ-
ence of nutrients into peoples diet were postulated, which
included (i) will gene expression in response to metabolic
process, at cellular level, influence the health of an individual?
(ii) Are gene expression and metabolic response the result of
the interaction between genotype and environment/nutrient?
(iii) Understanding how this interaction process occurs
between gene and nutrient could lead to the prescription of
specific diets for each individual. Hence, in order to answer
those questions, Nutrigenomics was introduced [2, 57]. The
studies on Nutrigenomics are focused on the effects of the
nutrients over the genome, proteome, and metabolome, as
illustrated on Figure 1 [2, 710].
molecular tools to search, access, and understand the several
responses obtained through a certain diet applied between
individuals or population groups [2, 5, 11, 12]. It seeks to
elucidate how the components of a particular diet (bioactive
compound) may affect the expression of genes, which may
have increased its potential or which can be suppressed [2,
5, 12]. This response will depend on how genes will show
a changed activity or alter gene expression (Figure 1) [2].
Some examples of this gene-nutrient interaction are their
capacity on binding to transcription factors. This binding
enhances or interferes with the ability of transcription factors
on interacting with elements that will lead to the binding
control of RNA polymerase. Earlier studies performed with
vitamins A, D and fatty acids have shown that they can trigger
direct actions in activating nuclear receptors and induce
gene transcription [5, 13, 14]. Compounds such as resveratrol
present in wine and soy genistein may indirectly influence
the molecular signaling pathways, such as the factor kappa B
[8, 13, 14]. The involvement of these factors in the activation
2 Journal of Nutrition and Metabolism
Nutrigenomics
Nutrigenetics
Nutrients Epigenomics
and
bioactive
compounds
of the foods Transcriptomics
Proteomics
Metabolomics
Figure 1: Omics sciences used in understanding the relationship between nutrition versus health versus disease (source: [4], with
modifications; [9] with modifications).
and regulation of key molecules is associated with diseases
ranging from inflammation to cancer [13, 14].
With information obtained from the HGP, it was found
that humans have 99.9% identity between their genomes. A
distinct difference between their weight, height, eye color/
hair, and other features is only 0.1% of the gene sequence
and this difference, among other factors, also determines the
nutritional requirements and the risk of developing some
of the NTCDs [2, 3, 16]. Single Nucleotide Polymorphisms
(SNPs) are the main reason for this genetic variation, and it
can often change the encoded protein [5, 17]. Studies have
shown that certain genes and their variants can be regulated
or are influenced by nutrients/food compounds from the
diet and that these molecular variations may have beneficial
actions to the health of an individual [2, 3, 17, 18].
1.1. From Nutrition to Nutrigenomics. Research on nutritional
area can be seen since 400 BC, when Hippocrates speculated
the hypothesis that the warm body temperature was innate.
Around 1700 AD, the so-called analytical Chemistry Era
began [12]. During this period, Lavoisier discovered how
food was metabolized by the body, generating water, carbon
dioxide, and energy [19]. In the 19th century, Liebig identified
carbohydrates, proteins, lipids, and other macronutrients that
released heat [12, 19]. During the next Era, called Chemical
and Analytical Era of Nutrition, which occurred between the
18th and 20th centuries, Antonie Lavoisier made important
discoveries on food metabolism and their relation with
energy production, including its relevance on breathing and
oxidation [12, 19]. Later, during the Biological Era, as the
19th century is known, studies on metabolism and chemistry
were done, helping the science of nutrition on defining
their role in the development and prevention of chronic
diseases, such as cancer, cardiovascular, neurodegenerative,
and bone metabolism disorders [12, 19]. Nowadays, the Pos-
Genomic Era is being experienced. This era is characterized
by the integration of three fields: biological, social, and
environmental, where scientific discoveries on nutritional
pathophysiology and metabolism are included [12, 19].
DNA
RNA
Phenotype
Protein
Metabolites
1.2. Nutrigenomics and Other Omics Sciences. After the HGP,
discussions and actions began on a new biological era, the
Post-Genomic Era, where the evolution of bioinformatics
provided advances in omics science research. These sciences
use biotechnology to isolate and characterize a greater num-
ber of biomolecules from the same group, such as DNA, RNA,
proteins, or metabolites. Hence, after Genomics, other Omic
Sciences appeared as revolutionary tools, such as Proteomics,
Metabolomics and Transcriptomics [8, 20].
Therefore, the first definition of Nutrigenomics referred
only to studies on the effects of nutrients/bioactive food on
gene expression of an individual. Nowadays, this definition
expanded and, recently, Nutrigenomics also involves the
studies on nutritional factors that act protecting the genome.
Thus, this new science seeks to understand the influence of
dietary components on the Genome, Transcriptome, Pro-
teome, and Metabolome [13]. Nutrigenomics, in a single
experiment, can generate multiple responses, so it is nec-
essary to be innovative in the approaches of this area [2].
Moreover, Nutrigenomics is able to extract useful biological
information from the data collected. The final answer can
only be achieved after a series of investigations or surveys
among different groups and teams. Therefore, there is a grow-
ing partnership between countries/teams/research groups,
involving Nutrition field, Biology, Medicine, Genomics, and
Bioinformation [1, 4, 5].
1.3. Nutritional Epigenomics. Epigenomics can be defined as
the study of the complete set of epigenetic modifications in
a cell or in a tissue at a given time [6, 21]. The epigenome
consists of chemical compounds that modify or mark the
genome in such way that it can indicate what a cell can
do and where and when to do it. These marks are called
epigenetic marks [6]. These epigenetic marks are passed
from one cell to another when they divide themselves and
thus will be passed from generation to generation. These
signatures are influenced by genotype in the surrounding
media (environment, diet, and drugs, e.g.) and will determine
the phenotype (Figure 1) [69].
Journal of Nutrition and Metabolism
1.4. Epigenetics. The epigenetic studies the modification of
DNA and proteins, linking the DNA and histones, which
may cause changes in chromatin structure without changing
the sequence of the nucleotides [7, 10]. Epigenetics is the
transmitted information based on gene expression as its
changes begin slowly but are progressive and potentially
reversible [7, 11]. An example is the folate metabolism, where
folic acid, which is a nutrient related to the genetic integrity,
ensures a balanced amount of deoxyribonucleotides for DNA
replication [2, 11]. It acts as a cofactor for enzymes associated
with the biosynthesis of nucleotides and thymidylate (protein
found in the RNA molecule), as universal donor of methyl
and DNA methylation reactions [7, 11].
Modulations in gene expression may be caused by epi-
genetic mechanisms through changes in chromosome struc-
ture [4, 12]. Examples are DNA methylation and histone
acetylation. Earlier studies have shown that DNA methy-
lation is directly related to the remodeling of chromatin
and this, in turn, is induced by the nutrient enzyme DNA
methyltransferase (DNMT), which catalyzes the transfer of
a methyl group from S-adenosylmethionine to specific sites
on the DNA [7, 12]. The S-adenosylmethionine metabolizes
compounds from food as folic acid, vitamins B6, B12, B2,
choline, and methionine [2, 12]. A deficiency of these can
lead to changes in carbon metabolism and thus impair DNA
methylation, increasing the risk of development of NTCD.
The DNA hypermethylation suppresses the gene responsible
for transcription, once hypomethylation is associated with
malignancies, such as prostate cancer and hepatocellular [4,
12].
1.5. Nutritional Transcriptomics. Transcriptomics studies the
complete set of activated RNA transcripts [11]. The mRNAs
are produced by a given moment and in a given tissue of a
selected organism; therefore, gene expression varies accord-
ing to the different circumstances and periods of time [8,
11]. Transcription factors, when activated, migrate to the
nucleus and bind to a specific sequence of DNA in the pro-
moter region of genes and, there, act by inhibiting or facili-
tating transcription [4, 8]. These transcription factors can be
stimulated by (i) physiological signals, such as those triggered
by nutrients/bioactive food compounds or the metabolites
resulting from them; (ii) hormones, pharmacological treat-
ments, and diseases, among others [8, 13]. They act as sensors
regulating/modulating transcription of the cells as needed
[13]. In nutrition research, transcriptomics can assist in
providing information about the mechanisms or underlying
effects of a particular nutrient or diet. It can also help
identifying genes, proteins, or metabolites that change in
the state of prediseases, as well as assisting on recognizing
and characterizing the pathways regulated by nutrients or
bioactive compounds in foods [8, 9, 11, 13].
1.6. Proteomics. Proteomics is the science that studies the
complete set of proteins involved in the biological processes
of a certain species [11, 21]. These proteins act in the cell, tis-
sue, or organ in its normal state, but in different physiological
or pathological situations, they may change their expression
3
level, or even their activity, likewise in transcriptomics [8, 11,
21].
Proteins are an important class of molecules that are
found in all living cells. They play a variety of roles in the cell
such as structural, mechanical, biochemical, cell signaling,
transport, and storage [2, 6]. They are also an essential part
of the human diet [2, 6]. The number of proteins produced
by an organism is much larger than the number of genes that
it possesses. This happens due to the numerous posttranscrip-
tional/translational modifications. Proteomics uses a set of
technologies designed to study the expression of proteins. For
this, it utilizes strategies, such as chromatographic techniques
associated with electrophoresis, prefractionation of samples
by extraction sequences, and organellar proteome analysis,
among others [3, 4, 8, 14]. Hence, Proteomics is a primordial
resource for Nutrigenomics, once that it is the gap between
genome sequences and cell behavior, becoming the biological
tool used to understand the process of genetic function
determination, and of how genome is activated in response to
certain diet [3, 4, 8, 14]. An example is the activity of butyrate,
which can alter the expression of several proteins from the
ubiquitin-proteasome system. This alteration suggests that
proteolysis can be the mechanism by which butyrate can
regulate key-proteins on the control of cell cycle, apoptosis,
and cell differentiation [4].
1.7. Metabolomics. Metabolome consists of a set of small pri-
mary/secondary metabolites and body fluids of an organism
or species. Metabolomics is the area of functional genomics
that studies the changes in metabolites, whose goal is to iso-
late and characterize them [1, 3, 22]. Research advances in this
area may facilitate the understanding of how the genotype
is related to the phenotype of an individual. Nutritionally,
metabolomics has many applications, once that it allows
knowing the arrangements and metabolic disorders caused
due to a persons diet and how these changes may affect the
ones health or disease [1, 3, 8, 16, 22]. Hence, metabolomics
also studies the metabolism under environmental and genetic
perturbations [11], which can be analyzed and interpreted
with the help of bioinformatics and statistical tools [11, 17].
The metabolites are dissolved in the cell cytosol and are
small organic molecules that interact directly with the pro-
teins and other macromolecules. They are divided into pri-
mary and secondary metabolites [1, 11, 22]. Primery metabo-
lites are directly involved with the routes of synthesis and
degradation of macromolecules, while secondary metabolites
are more common in plants and fungi, and act as structural
components and their defense [3, 22]. The metabolites in
living beings can act as substrates, such as inhibitors or
activators of an enzyme, molecular precursors, wastes of
synthesis, or degradation of macromolecules, among others
[3].
In the area of nutrition, metabolomics allows the under-
standing of metabolic arrangements and instabilities that
are the cause or suffer interference from the diet [1, 11].
This contributes to the knowledge of how the excess or lack
of some nutrients or compounds (secondary metabolites)
present in food can affect the health/illness of an individual.
4 Journal of Nutrition and Metabolism
These compounds (nutrients or not) interact in several ways
within the body, changing the metabolome pathways. As
an example, perilla alcohol (monoterpene extracted from
strawberry) can act as an anticancer molecule under certain
organic stimulations [1, 3].
1.8. Nutrigenomics and Nontransmissible Chromic Diseases
(NTCDs). Nutrition is the process that offers different sub-
stances to an organism that can work as energy supplier
(carbohydrate and fat), as cell structure sources (proteins),
and on metabolism control (vitamins and minerals), thus
maintaining its homeostasis [16]. The nutritional state of an
individual is the result of the interaction between various
factors, such as genetic background, physical body, and
emotional and social state [4]. Diet is a key role factor, once
those nutrients and other bioactive compounds present in
food can either be beneficial or initiate several diseases [4, 8,
16]. Among the illnesses related to food consumption, there
are the celiac disease, phenylketonuria, and NTCDs, such as
cancer, diabetes, and dislipidemies [8]. In this way, the health
state of a person will depend on the interaction between
their genes and their food diet [11]. Therefore, Nutrigenomics,
along with other omic sciences, aim to clarify the interaction
between genes and bioactive compounds from food sources
[4, 8, 11, 12, 16, 17].
1.9. Obesity. Researches have indicated that not only environ-
mental factors, but also genetics aspects are related to health
problems, including DCNTs and Metabolic Syndromes (MS)
[8, 23]. Recent studies showed that 80% of the difference
observed in the body mass index (BMI) of twins are related
to genetic factors [23]. As obesity causes a chronic process
of inflammation, the use of Nutrigenomics to modulate this
manner is highly promising [8]. Other reports demonstrated
that some food contain anti-inflammatory bioactives, such
as the caffeic acid (found in Yerba mate), tyrosol (found in
olive oil), quercetin (present in fruits and greeneries), and
lycopene (present in tomatoes, guavas, and watermelon).
These molecules act inhibiting the expression of COX2 and
iNOS genes through the reducing the translocation of the
Kappa-B nuclear factor from the cytoplasm to the nucleus
[8, 16].
There are several other ways where bioactive compounds
from food can interfere on genes. One of the primary mecha-
nisms for gene expression modulation is during transcription
[2, 4], where the synthesis of inflammatory mediators occurs
and has a fundamental role on numerous chronic illnesses,
including obesity [2, 4, 24]. Hence, interleukin-1 is one of
these mediators, which, after activation, stimulates the pro-
duction of many other molecules during the inflammation
cascade. The bioactive compound -tocoferol, found in green
tea, acts by decreasing the level of this chronic inflammatory
process that occurs in obese individuals. Therefore, studies
indicate that this component can assist on the treatment of
obesity [2, 24].
1.10. Cancer. The need for certain micronutrientes by the
organism depends on the persons age, genetic background,
and physical state [4, 25]. Earlier studies showed that the
deficiency of micronutrients, such as folic acid, vitamins B12,
B6, C, and E, selenium, niacin, and zinc can cause changes
into the DNA similar to what is seen after radiation exposure
[2, 4, 25]. These alterations can lead to the rupture of the DNA
double strand, oxidative lesions, or both. Furthermore, they
demonstrated to be narrowly related to the development of
cancer [25].
Moreover, molecules present in contaminated food can
produce toxic metabolites that may interact with DNA,
modifying its structure and inducing mutations. It is the case
of aflatoxin B1, which forms an adding compound able to
bind to the N-7 position of guanine residue, generating a
new product. This new molecule cleaves, then, the interaction
between one sugar and one nitrogenous base of a nucleotide,
leading to the formation of an apurinic site. The mutation can,
thus, cause severe damages on the liver, including necrosis,
cirrhosis, and carcinoma [7, 14].
During the metabolism of folate, the folic acid found
in food sources, is absorbed by the intestine and, through
many chemical processes of catabolism and synthesis, it
is transformed into 5-methyltetrahydrofolate. This chemical
component is necessary for the synthesis of methionine,
which in turn is used during the process of DNA mutilation.
Thus, a diet poor in folic acid can alter this process and
interfere on DNA replication, leading also to an increased risk
of cancer development [24, 25].
Nevertheless, various minerals work as protectors against
cancer development [25]. Among them, there are (i) sele-
nium, which stimulates the production of glutathione peroxi-
dase enzyme that acts on the reduction of hydrogen peroxide
and maintain the integrity of cell membranes; (ii) prosta-
cyclins, which decrease the oxidative damage of important
molecules, such as DNA, lipids, and lipoproteins; (iii) zinc,
which act on processes for the maintenance of genomic sta-
bility, genetic expression, and apoptosis modulation [3, 25].
1.11. Type II Diabetes. Diabetes counts for more than 90%
of all diseases of the world [2]. Type II Diabetes is a multi-
factorial pathogenesis that involves the interaction between
genetics and environmental factors [23]. Genomics studies
showed that there are 65 SNPs associated with the risk of
developing type II Diabetes [26].
With the advances of genome sequencing and the decod-
ing of the human genome, tests for the detection of SNPs
related to Type II Diabetes became available to the public. In
these exams, the patient is able to know it there is a genetic
predisposition to develop the disease [26]. However, caution
must be taken on applying this test for clinical practice,
once that studies have shown that patients that had negative
results on this exam for the presence of Type II Diabetes
SNPs felt so secure about it that they stopped taking care of
their food diets. Consequently, some later developed Diabetes
due to food income and insulin tolerance [26]. Nevertheless,
patients who received a positive result for the presence of
type II Diabetes change their life style, especially in their food
intake, which later decreased the development of the disease
by this group [26].
Journal of Nutrition and Metabolism 5

Table 1: Classification of Ronteltap and colleagues [15], showing the new marketing strategies into nine business models.

Business model Marketing strategy

Orientation according to
Shared responsibility between employer and employee, where a healthy lifestyle can contribute to a
the lifestyle of the
better productivity.
individual
We are togheter and
Improve the lifestyle with the help of social groups.
strong
Based on a set of changes into the lifestyle, including physical activities, diet therapies, and use of food
Gyms
supplement, among others.
Do a healthy diet This model offers a diagnostic tool where, based on the persons food ingestion, it can create a diet
yourself plan to improve a healthy diet.
Similar to the 4th plan reported above. In this, the person describes the food intake but also some
In, out
phenotype parameters in order to receive diet counseling.
Test and execute until Offers an interactive feedback about a persons health progress, which allows toadjust the diet
the end counseling as needed.
Inclusion of genetic information, data about food intake, and the persons phenotype, in order to
Orientation about the
obtain a personalized counseling on lifestyle, diet terapy, control of stress activity, and time
lifestyle
management.
In person treatment, where anthropometric data and food consumption of the cliente are obtained by
Face to face
a face-to-face interview.
We tell you Use of mass media as a healthy diet education method.

2. Conclusion and Perspectives
Nutrigenomics shows a new way of working with nutrition
and now, the knowledge of how food interferes with the
genetic code and how the organism responds to these
interferences and with the phenotype can be clarified.
Furthermore, the development inside Nutrition Sciences,
together with communication and marketing fields, provided
the emergence of a personalized nutritional counseling based
in Nutrigenomics. After analysis, it was observed that nine
different models can be built (Table 1).
Moreover, other sophisticated programs are available,
where it is even possible to obtain a nutritional counseling
based on the clients DNA. In this way, Gollust et al. [27]
published a report where he studied the intention of patients
on using online hypothetic programs for personalized nutri-
tional counseling. During the research, the patients described
that the presence of a physician during the nutritional
evaluation and the compilation of data into the program
was essential to bring a trusting diet plan and nutritional
counseling through the online system [27].
Furthermore, in order to evaluate the impact of personal
genomics to the population, a study placed in The United
States of America intended to analyze the motivation, knowl-
edge, risks, and benefits of sharing personal data to build a
personalized field of every individuals health condition [27].
Hence, it was observed that 92% of the interviewed ones were
willing to share their personal information to professional
of health area, while 32% considered themselves unaware of
what a genomic evaluation could do to their personal data
[27].
Henceforward, the recent advances on Nutrition Sciences
allow the application of a personal counselling, in contrary to
the general use of standard nutritional diets that was being
applied for many years. The personalized nutritional coun-
seling can be used not only to change diet habits and improve
life style, but also mainly will permit a better diagnostic of
certain diseases, retard the evolution of chronic illnesses, and
assist on the treatment of others. Although Nutrigenomics
is already available for clinical use, there are still few places
applying this tool in the heatlh field [15].
Since the introduction of Nutrigenomics into the omics
group, there was an upgrade of how physicians and other pro-
fessionals on evaluating and treating different diseases, espe-
cially DCTNs. Nevertheless, there is still a long way to go on
Nutrigenomics, as further research needs to be done in order
to connect a patients symptons/diseases with their genetic
profile, food diet, and environmental habits.
Moreover, with the knowledge integration of technologies
into health sciences, novel business models for personalized
nutritional counseling were highlighted, based on the per-
sons DNA. In this way, entities connected to the health system
must act in order to regulate these business models in order to
preserve the integrity of patients, increasing the performance
of the system for nutritional orientation.
Therefore, scientists and professionals of human health
sciences can constantly contribute to Nutrigenomics through
research and on the development of new tools that can assist
on a better quality of life and healthy diet to the population.
Conflict of Interests
The authors declare that there is no conflict of interests
regarding the publication of this paper.
6 Journal of Nutrition and Metabolism

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